Abstract
Intralesional therapy of melanoma patients with locally advanced metastatic disease is attracting increasing interest, not least due to its ability to lead to both direct tumor cell killing and the stimulation of both a local and a systemic immune response. An obvious pre-requisite for this type of approach is the presence of accessible metastases that are amenable to direct injection with the therapeutic agent of interest. Patients who present with these characteristics belong to stages IIIB/C or IV of the disease. Surgical resection with intention to cure is the standard of care for patients with limited tumor burden and confined spread of disease (resectable patients). However, this category of patients is at a high risk of further recurrences until the disease becomes inoperable (unresectable) or progresses to a more advanced stage with visceral organ involvement, after which the prognosis is particularly grim. Most of the intralesional treatments tested so far, including the recently approved oncolytic virus talimogene laherparepvec, target the subpopulation of patients with unresectable disease, but the possibility to use the intralesional treatment in a neoadjuvant setting for fully resectable patients is attracting considerable interest. The present article reviews approved products and advanced stage pharmaceutical agents in development for the intralesional treatment of melanoma patients.
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Abbreviations
- AEs:
-
Adverse events
- CR:
-
Complete responses
- CTLA-4:
-
Cytotoxic T lymphocyte antigen 4
- DLT:
-
Dose-limiting toxicity
- DPCP:
-
Diphencyprone
- ECOG:
-
Eastern Cooperative Oncology Group
- EMA:
-
European medicine agency
- FDA:
-
Food and drug administration
- IFNa:
-
Interferon α
- IFNb:
-
Interferon β
- IL2:
-
Interleukin-2
- ILP:
-
Isolated limb perfusion
- irRC:
-
Immune-related response criteria
- ITT:
-
Intention-to-treat
- OR:
-
Objective response
- ORR:
-
Objective response rate
- PFS:
-
Progression-free survival
- PR:
-
Partial response
- PV-10:
-
Rose Bengal (Provectus)
- RFS:
-
Recurrence-free survival
- TLR7:
-
Toll-like receptor 7
- TNF:
-
Tumor necrosis factor α
- T-Vec:
-
Talimogene laherparepvec, Imlygic™ (Amgen)
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Support from the Swiss Federal Institute of Technology Zurich (ETHZ), the Swiss National Science Foundation (SNF) and from European Research Council (ERC) Advanced Grant (ZAUBERKUGEL) is gratefully acknowledged.
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B. Weide declares receiving commercial research grants from Bristol-Myers Squibb (BMS) and Merck Sharp and Dohme (MSD), having received travel/accommodation expenses from BMS, MSD, Roche, Amgen, Philogen, Curevac and compensation for advisory services from MSD, BMS, Philogen, and Curevac. D. Neri is co-founder and shareholder of Philogen S.p.A. G. Elia declares no conflict of interest.
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This paper is a Focussed Research Review based on a presentation given at the Fourteenth Annual Meeting of the Association for Cancer Immunotherapy (CIMT), held in Mainz, Germany, 10th–12th May, 2016. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.
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Weide, B., Neri, D. & Elia, G. Intralesional treatment of metastatic melanoma: a review of therapeutic options. Cancer Immunol Immunother 66, 647–656 (2017). https://doi.org/10.1007/s00262-016-1952-0
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DOI: https://doi.org/10.1007/s00262-016-1952-0